大龄妇女高危型人乳头瘤病毒感染特征及影响因素的前瞻性研究

Carcinogenic cervical human papillomavirus (HPV) persistent infection is the prerequisite of cervical cancer. HPV vaccines have been widely used outside China, the attitudes toward immunization strategies in adult women older than 26 years remain disconcordant. Data of cross sectional studies showed that the epidemiological style of HPV infection in China is different from those of the developed countries. In developed countries, the prevalences of high risk HPV DNA peak shortly after the debut of sexual activity (16-20 years old), and then quickly decrease and keep at low rate. While in Chinese women, the age-specific prevalences of HPV DNA present as double peak, the first peak appears at 15 - 24 years old and the second peak at 35 - 39 years old. There was difference between rural and urban area. The characteristics of persistence, clearance and clinical outcome after carcinogenic HPV infection remain unknown. Our team would prospectively follow up healthy women aged 18 - 45 years old. Based on the collected sequential cervical swabs of the participants, the characteristics of carcinogenic cervical HPV infection among women of different living areas or different age groups, including the prevalence and incidence of high risk HPV infection, the duration of persistence would be studied, the cumulative incidences of developing into persistent infection or cervical intraepithelial neoplasia 2 plus (CIN2+) from prevalent or newly acquired high risk HPV infection as well as the risk factors would be carefully investigated. Also, the potential value of HPV 16/18 E6 antibodies as indicator for the outcome of HPV 16/18 persistent infection or HPV 16/18 related CIN2+ would be analyzed. The data form this study would support making the immunization policies suitable for Chinese women of different age groups.

高危型人乳头瘤病毒（HPV）的持续性感染是宫颈癌发生的必要条件。宫颈癌疫苗已在国外广泛应用，对26岁以上大龄女性的免疫策略尚存争议。我国HPV感染特征与发达国家有较大差异，发达国家HPV阳性率在性生活开始后数年内达到高峰，而后快速下降并在大龄女性中保持较低感染率，而我国则呈现双峰态势，在大龄女性中感染率出现第二高峰，且存在城乡差异。我国大龄女性中高危型HPV感染后的清除及疾病转归的特征尚不明确。本课题拟通过对18-45岁健康女性的长期随访，深入研究城乡/年龄别高危型HPV感染特征，包括基线感染率、新感染率、感染维持时间等，明确基线及新感染者中转化为持续性感染及高度子宫内皮瘤样病变或原位癌（CIN2+）的风险，分析影响感染转归的危险因素，同时探索E6抗体做为预测发生HPV型相关持续性感染及CIN2后疾病转归的临床指导意义，为制定我国宫颈癌防控策略提供科学依据。

高危型人乳头瘤病毒（HR-HPV）的持续性感染是宫颈癌发生的必要条件。宫颈癌疫苗已在国外广泛应用，对26岁以上大龄女性的免疫策略尚存争议。2020年美国HPV疫苗接种指南指出27岁及以上人群接种HPV疫苗的卫生经济效益有限，不推荐27岁及以上人群接种HPV疫苗。我国HPV感染特征与发达国家有较大差异，研究显示，发达国家HPV阳性率在性生活开始后数年内达到高峰，而后快速下降并在大龄女性中保持较低感染率，而我国横断面调查结果显示HPV感染呈现双峰态势，在大龄女性中感染率出现第二高峰。中国女性人群中高危型别HPV感染、感染的持续时间以及临床结局在不同年龄中是否存在差异，尚缺乏高质量前瞻性研究的数据。.通过长期随访和比较分析，本课题获得我国女性HR-HPV感染特征为：.1）.我国自然女性人群中，HR-HPV感染呈现双峰态势，18-26岁年轻女性HR-HPV感染率与27-45岁大龄女性相近，无统计学差异（14.78% VS 14.23%，P>0.05）。大龄女性细胞学异常率高于年轻女性（6.37% VS 5.43%，P=0.0267）；子宫颈高度癌前病变（CIN2+）患病率略高于年轻女性，但差异无统计学意义（1.59% VS 0.96%，P>0.05） .2）.我国自然女性人群中，与18-26岁年轻女性相比，27-45岁大龄女性HR-HPV新发感染率、6m持续性感染率、12m持续性感染率和高危型别相关的CIN2+发病率略低，但均无统计学差异。年轻女性高危型HPV相关的宫颈癌前病变（CIN1+）发病率高于大龄女性（RR=1.70，95%CI：1.09-2.66）。我国大龄女性HR-HPV感染风险仍然较高；.3）.27-45岁大龄女性与18-26岁年轻女性对HR-HPV清除率及中位清除时间无统计学差异。.本研究揭示了我国27-45岁大龄女性和18-26岁年轻女性高危型别HPV基线感染、新发感染、持续性感染和清除率等感染特征，为开展基于我国流行病学特征的HPV疫苗卫生经济学评价提供了重要的基础数据，为制定适合我国女性人群的宫颈癌预防与控制策略的制订提供了科学依据。